This project is aimed at learning about he pathogenesis of inflammatory eye diseases which are designated "uveitis". In experiments with human material we have found that by using a sensitive assay, lymphocytes from a portion of healthy donors react in culture to retinal-specific antigens, S-antigen (S-Ag) and interphotoreceptor retinoid-binding protein (IRBP). Furthermore, clones of lymphocytes with specificity toward S-Ag were cultivated from the blood of a healthy donor. It is proposed that such lymphocytes, when activated, could play a pivotal role in the pathogeneis of uveitic conditions. The major segment of this project has focused on the animal disease, experimental autoimmune uveitis (EAU), which is considered a model for certain human conditions. Main findings: (1) Bovine IRBP is highly uveitogenic in primates, while monkey IRBP did not induce EAU at similar doses. Antibodies from monkeys immunized with bovine IRBP cross reacted well with monkey IRBP but the cross reaction was poorly detected by cellular reactions. (2) Fragments of IRBP of known amino acid sequence were found highly uveitogenic in rats, thus making it possible to identify the uveitogenic site(s) of this molecule. (3) A cell line of rat lymphocytes specific for IRBP was established in culture. The line cells produced EAU at numbers as low as 500,000/rat and will be useful for future studies on the pathogenesis of this disease. (4) Rats of the W/F inbred strain are poor responders to S-Ag induced EAU. This low susceptibility was found to be due to a poorly developed cellular immune response to S-Ag. (5) EAU develop ment was found to be markedly enhanced by local damage to rat eyes. The data suggest that local injury could facilitate immune-mediated inflammation in the human eye as well. (6) Animals immunized with IRBP or S-Ag develop pinealitis, in addition to uveitis. The type of inflammation is different, however, in the two organs of affected rats and we report here that the "acute" inflammation in the eye disappears within 10 days while the "chronic" infiltration in the pineal lasts for at least 3 months.